Cargando…

Sphingosine Kinase 1 in Breast Cancer—A New Molecular Marker and a Therapy Target

It is now well-established that sphingosine kinase 1 (SK1) plays a significant role in breast cancer development, progression, and spread, whereas SK1 knockdown can reverse these processes. In breast cancer cells and tumors, SK1 was shown to interact with various pathways involved in cell survival a...

Descripción completa

Detalles Bibliográficos
Autores principales: Alshaker, Heba, Thrower, Hannah, Pchejetski, Dmitri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098968/
https://www.ncbi.nlm.nih.gov/pubmed/32266132
http://dx.doi.org/10.3389/fonc.2020.00289
_version_ 1783511260106588160
author Alshaker, Heba
Thrower, Hannah
Pchejetski, Dmitri
author_facet Alshaker, Heba
Thrower, Hannah
Pchejetski, Dmitri
author_sort Alshaker, Heba
collection PubMed
description It is now well-established that sphingosine kinase 1 (SK1) plays a significant role in breast cancer development, progression, and spread, whereas SK1 knockdown can reverse these processes. In breast cancer cells and tumors, SK1 was shown to interact with various pathways involved in cell survival and chemoresistance, such as nuclear factor-kappa B (NFκB), Notch, Ras/MAPK, PKC, and PI3K. SK1 is upregulated by estrogen signaling, which, in turn, confers cancer cells with resistance to tamoxifen. Sphingosine-1-phosphate (S1P) produced by SK1 has been linked to tumor invasion and metastasis. Both SK1 and S1P are closely linked to inflammation and adipokine signaling in breast cancer. In human tumors, high SK1 expression has been linked with poorer survival and prognosis. SK1 is upregulated in triple negative tumors and basal-like subtypes. It is often associated with high phosphorylation levels of ERK1/2, SFK, LYN, AKT, and NFκB. Higher tumor SK1 mRNA levels were correlated with poor response to chemotherapy. This review summarizes the up-to-date evidence and discusses the therapeutic potential for the SK1 inhibition in breast cancer, with emphasis on the mechanisms of chemoresistance and combination with other therapies such as gefitinib or docetaxel. We have outlined four key areas for future development, including tumor microenvironment, combination therapies, and nanomedicine. We conclude that SK1 may have a potential as a target for precision medicine, its high expression being a negative prognostic marker in ER-negative breast cancer, as well as a target for chemosensitization therapy.
format Online
Article
Text
id pubmed-7098968
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-70989682020-04-07 Sphingosine Kinase 1 in Breast Cancer—A New Molecular Marker and a Therapy Target Alshaker, Heba Thrower, Hannah Pchejetski, Dmitri Front Oncol Oncology It is now well-established that sphingosine kinase 1 (SK1) plays a significant role in breast cancer development, progression, and spread, whereas SK1 knockdown can reverse these processes. In breast cancer cells and tumors, SK1 was shown to interact with various pathways involved in cell survival and chemoresistance, such as nuclear factor-kappa B (NFκB), Notch, Ras/MAPK, PKC, and PI3K. SK1 is upregulated by estrogen signaling, which, in turn, confers cancer cells with resistance to tamoxifen. Sphingosine-1-phosphate (S1P) produced by SK1 has been linked to tumor invasion and metastasis. Both SK1 and S1P are closely linked to inflammation and adipokine signaling in breast cancer. In human tumors, high SK1 expression has been linked with poorer survival and prognosis. SK1 is upregulated in triple negative tumors and basal-like subtypes. It is often associated with high phosphorylation levels of ERK1/2, SFK, LYN, AKT, and NFκB. Higher tumor SK1 mRNA levels were correlated with poor response to chemotherapy. This review summarizes the up-to-date evidence and discusses the therapeutic potential for the SK1 inhibition in breast cancer, with emphasis on the mechanisms of chemoresistance and combination with other therapies such as gefitinib or docetaxel. We have outlined four key areas for future development, including tumor microenvironment, combination therapies, and nanomedicine. We conclude that SK1 may have a potential as a target for precision medicine, its high expression being a negative prognostic marker in ER-negative breast cancer, as well as a target for chemosensitization therapy. Frontiers Media S.A. 2020-03-20 /pmc/articles/PMC7098968/ /pubmed/32266132 http://dx.doi.org/10.3389/fonc.2020.00289 Text en Copyright © 2020 Alshaker, Thrower and Pchejetski. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Alshaker, Heba
Thrower, Hannah
Pchejetski, Dmitri
Sphingosine Kinase 1 in Breast Cancer—A New Molecular Marker and a Therapy Target
title Sphingosine Kinase 1 in Breast Cancer—A New Molecular Marker and a Therapy Target
title_full Sphingosine Kinase 1 in Breast Cancer—A New Molecular Marker and a Therapy Target
title_fullStr Sphingosine Kinase 1 in Breast Cancer—A New Molecular Marker and a Therapy Target
title_full_unstemmed Sphingosine Kinase 1 in Breast Cancer—A New Molecular Marker and a Therapy Target
title_short Sphingosine Kinase 1 in Breast Cancer—A New Molecular Marker and a Therapy Target
title_sort sphingosine kinase 1 in breast cancer—a new molecular marker and a therapy target
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098968/
https://www.ncbi.nlm.nih.gov/pubmed/32266132
http://dx.doi.org/10.3389/fonc.2020.00289
work_keys_str_mv AT alshakerheba sphingosinekinase1inbreastcanceranewmolecularmarkerandatherapytarget
AT throwerhannah sphingosinekinase1inbreastcanceranewmolecularmarkerandatherapytarget
AT pchejetskidmitri sphingosinekinase1inbreastcanceranewmolecularmarkerandatherapytarget